Gut microbiome partially mediates and coordinates the effects of genetics on anxiety-like behavior in Collaborative Cross mice

Growing evidence suggests that the gut microbiome (GM) plays a critical role in health and disease. However, the contribution of GM to psychiatric disorders, especially anxiety, remains unclear. We used the Collaborative Cross (CC) mouse population-based model to identify anxiety associated host gen...

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Vydáno v:Scientific reports Ročník 11; číslo 1; s. 270 - 13
Hlavní autoři: Jin, X., Zhang, Y., Celniker, S. E., Xia, Y., Mao, J.-H., Snijders, A. M., Chang, H.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 11.01.2021
Nature Publishing Group
Nature Portfolio
Témata:
631/208/1515
631/326/2565/2134
Anxiety
Association analysis
BASIC BIOLOGICAL SCIENCES
Behavioural genetics
Collaboration
Digestive system
Genetic analysis
Genetics
Genomes
Gut microbiota
Humanities and Social Sciences
Intestinal microflora
Mental disorders
Microbiome
Microbiomes
Microbiota
multidisciplinary
Phenotypes
Science
Science (multidisciplinary)
Single-nucleotide polymorphism
ISSN:2045-2322, 2045-2322
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Popis
Shrnutí:Growing evidence suggests that the gut microbiome (GM) plays a critical role in health and disease. However, the contribution of GM to psychiatric disorders, especially anxiety, remains unclear. We used the Collaborative Cross (CC) mouse population-based model to identify anxiety associated host genetic and GM factors. Anxiety-like behavior of 445 mice across 30 CC strains was measured using the light/dark box assay and documented by video. A custom tracking system was developed to quantify seven anxiety-related phenotypes based on video. Mice were assigned to a low or high anxiety group by consensus clustering using seven anxiety-related phenotypes. Genome-wide association analysis (GWAS) identified 141 genes (264 SNPs) significantly enriched for anxiety and depression related functions. In the same CC cohort, we measured GM composition and identified five families that differ between high and low anxiety mice. Anxiety level was predicted with 79% accuracy and an AUC of 0.81. Mediation analyses revealed that the genetic contribution to anxiety was partially mediated by the GM. Our findings indicate that GM partially mediates and coordinates the effects of genetics on anxiety.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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National Institute of Environmental Health Sciences (NIEHS)
National Cancer Institute (NCI)
National Institutes of Health (NIH)
USDOE Office of Science (SC), Biological and Environmental Research (BER)
USDOE Laboratory Directed Research and Development (LDRD) Program
National Natural Science Foundation of China (NSFC)
AC02-05CH11231; DE AC02-05CH11231
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-79538-x